Sonogashira diversification of unprotected halotryptophans, halotryptophan containing tripeptides; and generation of a new to nature bromo-natural product and its diversification in water.

The blending together of synthetic chemistry with natural product biosynthesis represents a potentially powerful approach to synthesis; to enable this, further synthetic tools and methodologies are needed. To this end, we have explored the first Sonogashira cross-coupling to halotryptophans in water. Broad reaction scope is demonstrated and we have explored the limits of the scope of the reaction. We have demonstrated this methodology to work excellently in the modification of model tripeptides. Furthermore, through precursor directed biosynthesis, we have generated for the first time a new to nature brominated natural product bromo-cystargamide, and demonstrated the applicability of our reaction conditions to modify this novel metabolite.

Determination of short-term exposure with a direct reading photoionization detector.

The use of a direct reading photoionization detector (PID) to determine short-term solvent exposures is described in the present paper. To assess the relevance of such a total exposure evaluation it was necessary to compare it with the real concentration of pollutants. This comparison was made by measuring in parallel with the PID determination the concentration of each pollutant using a standard technique, i.e. sampling on charcoal tubes and subsequent analysis by gas chromatography. Laboratory tests showed that the linearity of the answer of the PID is good for many compounds and for a mixture of these compounds. Similar tests were carried out for painters in workplaces with the same good correlations (determination coefficient r2 close to 1) between the PID response and the real concentration of the pollutants measured on the sampling tubes. The use of PID also allowed determination of the exposure profile of the workers and comparison of the short-term exposure to the corresponding limit values. Many cases of the short-term limit values being exceeded were revealed by use of the PID, although very few cases of the long-term limit values have been found by the usual sampling (charcoal tube) and analytical (gas chromatography) methods.

Estimation of the percutaneous absorption of styrene in an industrial situation.

OBJECTIVE: This field study was designed to compare the level of styrene absorbed percutaneously with that absorbed by inhalation in a real situation in the fiberglass-reinforced polyester industry. METHODS: The study protocol consisted of comparisons of the patterns of urinary excretion of styrene metabolites by four groups of workers, all of whom performed the same task at the same time in the same workshop but wore the following different protective equipment: total protection with an insulating suit and mask, respiratory equipment only, percutaneous protection only, and no protection. RESULTS: The urinary excretion level of the group with total protection did not significantly differ from that of the group with respiratory protection only. CONCLUSIONS: Precutaneous absorption is not a particularly important pathway for styrene absorption during stratification work in the polyester industry. Completely insulating personal protective equipment provides no greater level of protection than does a respirator at positive pressure alone.

[Towards a new vaccine economy?]. / Vers une nouvelle économie du vaccin?

When Jonas Salk announced in the mid-50s the availability of a new vaccine against poliomyelitis, the world had the impression that it was now controlling infectious diseases. In fact, the success of this vaccine has been considerable and although some innovations lead to the launch of vaccines against flu, measles, rubella or mumps, the world vaccine market remained remarkably stable till the mid-80s. However, since 1984 (launch of the hepatitis B vaccine) there have been very substantial changes and further change is expected in the next ten years in the world market. Today, big companies are making a concentrated supply: Pasteur Mérieux with its subsidiary Connaught, SmithKline Beecham who acquired the Belgian company RIT, and Merck & Co. who is joining its forces with Pasteur Mérieux. Medium sized and small companies remain and reflect the situation of the past, but must work hard to secure their long term existence eventhough the world demand is going to double before the year 2000. Very substantial technological innovations explain to a large extent the development of the supply: progress in molecular biology, and particularly genetic engineering, lead to recombinant vaccines of which hepatitis B is the best example with worldwide sales in the range of $600 million a year. Similarly, conjugation technologies have allowed the development of new vaccines against meningitis, particularly Haemophilus influenzae type b. More recently, an efficacious vaccine against hepatitis A has been launched and many new products will be marketed in the next years against herpes, Lyme disease, and agents of other meningitis, etc.(ABSTRACT TRUNCATED AT 250 WORDS)

Occupational exposure to organic solvents during paint stripping and painting operations in the aeronautical industry.

The exposure of workers to methylene chloride and phenol in an aeronautical workshop was measured during stripping of paint from a Boeing B 747. Methylene chloride exposure was measured during two work days by personal air sampling, while area sampling was used for phenol. During paint stripping operations, methylene chloride air concentrations ranged from 299.2 mg/m3 (83.1 ppm) to 1888.9 mg/m3 (524.7 ppm). The exposures to methylene chloride calculated for an 8-h work day ranged from 86 mg/m3 (23.9 ppm) to 1239.5 mg/m3 (344.3 ppm). In another aeronautical workshop, exposure to organic solvents, especially ethylene glycol monoethylether acetate (EGEEA), was controlled during the painting of an Airbus A 320. The external exposure to solvents and EGEEA was measured by means of individual air sampling. The estimation of internal exposure to EGEEA was made by measuring its urinary metabolite, ethoxyacetic acid (EAA). Both measurements were made during the course of 3 days. The biological samples were taken pre- and post-shift. During painting operations, methyl ethyl ketone, ethyl acetate, n-butyl alcohol, methyl isobutyl ketone, toluene, n-butyl acetate, ethylbenzene, xylenes and EGEEA were detected in working atmospheres. For these solvents, air concentrations ranged from 0.1 ppm to 69.1 ppm. EGEEA concentrations ranged from 29.2 mg/m3 (5.4 ppm) to 150.1 mg/m3 (27.8 ppm). For biological samples, the average concentrations of EAA were 108.4 mg/g creatinine in pre-shift and 139.4 mg/g creatinine in post-shift samples. Despite the fact that workers wore protective respiratory equipment during paint spraying operations, EEA urinary concentrations are high and suggest that percutaneous uptake is the main route of exposure for EGEEA.(ABSTRACT TRUNCATED AT 250 WORDS)